Pharmacokinetics of Pars Plana Intravitreal Injections versus Microcannula Suprachoroidal Injections of Bevacizumab in a Porcine Model

Abstract

Direct intravitreal injection of bevacizumab has a more sustained pharmacologic profile than does a similar dose delivered to the suprachoroidal space. Intravitreal injections distributed more to the inner retina, whereas suprachoroidal delivery occurred primarily at the choroid, retinal pigment epithelium, and photoreceptor outer segments. Sustained release formulation of larger biological molecules should be considered to optimize suprachoroidal delivery. Inflammation from injections is granulomatous, seen only with intravitreal injections, and may result from either an altered immune response or a dose-related effect.

Hyperoxia Causes Regression of Vitreous Neovascularization by Downregulating VEGF/VEGFR2 Pathway

“…Here we provide the first evidence that HT causes rapid regression of established vitreous NV while sparing existing intraretinal vessels involved in revascularization. Unlike VEGF trap, which caused some retinal inflammation as noted by us and by others previously, 38 HT actually suppressed inflammation similar to when HT was used in the preproliferative phase of ischemic retinopathy. 19 Together with previous studies showing beneficial effects when oxygen is supplied during the preproliferative phase of ischemic retinopathy, [17][18][19] the present study indicates a broad therapeutic time window for HT and warrants further investigation of the beneficial actions of HT in ischemic retinopathy.…”

Safety and pharmacodynamics of suprachoroidal injection of triamcinolone acetonide as a controlled ocular drug release model

“…Understanding its delivery mechanism and possible lateral side effects is the first step to deploy this technology. So far, a few reports are available using either cannulation or proprietary hollow microneedle [11,13,30]. The current study demonstrates that suprachoroidal injection is feasible with a 30 gauge sharp needle attached to a Hamilton syringe loaded on a repeating dispenser.…”

“…Olsen et al cannulated pig suprachoroidal space and injected 70 μL of bevacizumab mixed with hyaluronic acid (50 μL bevacizumab + 20 μL of hyaluronic acid). Ocular pharmacokinetics was reported without mentioning any complication [13]. In the case of the pig, the vitreous volume is more than double the volume of rabbit vitreous [31].…”

“…For example, the amount of Avastin reaching the retina from suprachoroidal delivery was limited and cleared more quickly compared with intravitreal delivery [13]. In contrast, sodium fluorescein seems to behave differently [11,12].…”

Clinical Application of Drug Delivery Systems for Treating AMD

“…The pharmacokinetic study of suprachoroidal delivery of TA in pigs has shown that TA remained in the ocular tissues for at least 120 days, and the systemic exposure was very low (Olsen et al, 2006). In contrast, the study to compare the pharmacokinetics of bevacizumab between intravitreal and suprachoroidal injections to pigs (Olsen et al, 2011) reported that the profile of intravitreal injections of bevacizumab was more sustained than that of suprachoroidal injections at the same dosage level. Intravitreal injected bevacizumab distributed more to the inner retina, whereas suprachoroidal injected bevacizumab distributed primarily to the choroid, RPE, and photoreceptor outer segments.…”